Two of the potential obstacles precluding inclusion of higher levels of dry distillers grains with solubles (DDGS) in corn-based dairy cow diets are the low levels of rumen-degradable protein (RDP) and the fatty acid content and composition of DDGS. Therefore, the objective of this experiment was to evaluate the production and rumen responses to dietary alterations in the level of RDP and DDGS for dairy cows fed a high corn silage diet. The experimental design was a replicated 4×4 Latin square with 21-d periods: 14 d of adaptation and 7 d of sampling; 16 uncannulated cows and 4 ruminally cannulated cows were blocked and assigned randomly to treatment sequences. Rations were provided as total mixed rations and were formulated to be high or low in RDP, with or without DDGS replacing soybean-based concentrates: high RDP, no DDGS (HRDP0); low RDP, no DDGS (LRDP0); low RDP, 10% DDGS; and low RDP, 20% DDGS. Body weight (696kg) and dry matter intake (26.6 kg/d) were not affected by treatment. Rumen ammonia concentration was greater for HRDP0 than LRDP0, but was unaffected by level of DDGS inclusion. The mean and minimum rumen pH and time pH was <5.5 were not different between diets. Milk production tended to be lower for cows fed HRDP0 than LRDP0 and tended to be linearly reduced as DDGS inclusion increased. Milk protein yield tended to be greater for cows fed LRDP0 than HRDP0, but was unaffected by DDGS level. Milk fat production, concentration, and fat-corrected milk were linearly reduced by increasing levels of DDGS. Based on these results, feeding DDGS at 20% of diet dry matter is not recommended for diets based on high corn silage.